Osthole protects against inflammation in a rat model of chronic kidney failure via suppression of nuclear factor-κB, transforming growth factor-β1 and activation of phosphoinositide 3-kinase/protein kinase B/nuclear factor (erythroid-derived 2)-like 2 signaling

Multiple pharmacological applications of osthole have been previously recognized, including antioxidant, anti-inflammatory, anti-platelet and estrogenic effects, and resistance to pain. The present study investigated the protective effects of osthole against inflammation in a rat model of chronic kidney failure (CRF) and the underlying mechanisms. Osthole treatment with significantly reversed CRF-induced changes in serum creatinine, calcium, phosphorus and blood urea nitrogen levels in CRF rats. Male Sprague-Dawley rats (age, 8 weeks) received 200 mg/kg 2% adenine suspension to induce CRF in the model group. In the osthole-treated group, rats received 200 mg/kg 2% adenine suspension + osthole (40 mg/kg, intravenously). The results revealed that treatment with osthole significantly inhibited CRF-induced tumor necrosis factor-a, interleukin (IL)-8 and IL-6 expression, and suppressed nuclear factor-kappa B (NF-kappa B) protein expression in CRF rats. Osthole treatment significantly attenuated the protein expression of transforming growth factor-beta 1 (TGF-beta 1), reduced monocyte chemoattractant protein-1 activity and increased the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) ratio in CRF rats. These results suggested that osthole protects against inflammation in a rat model of CRF via suppression of NF-kappa B and TGF-beta 1, and activation of PI3K/Akt/nuclear factor (erythroid-derived 2)-like 2 signaling. Therefore, osthole may represent a potential therapeutic agent for the treatment of CRF.